title: Distinct functional stoichiometry of potassium channel beta subunits.
abstract: Shaker-type potassium channels play important roles in determining the electrical excitability of cells. The native channel complex is thought to be formed by four pore-forming alpha subunits that provide four interaction sites for auxiliary modulatory Kvbeta subunits. Because Kvbeta subunits possess diverse modulatory activities including either up-regulation or down-regulation of potassium currents, differential assembly of the alpha-beta complex could give rise to diverse current properties. However, the detailed physical and functional stoichiometry of the alpha-beta complex remains unknown. Kvbeta1 subunits reduce potassium currents through inactivation, whereas Kvbeta2 subunits enhance potassium currents by inhibiting the Kvbeta1-mediated inactivation and at the same time by promoting the surface expression of certain potassium channels. In this report we show that Kvbeta1 and Kvbeta2 of the Shaker-type potassium channels display distinct functional stoichiometry to interact with the Kv1 alpha subunits, a subfamily of Shaker-type potassium channels. The interaction of Kvbeta1 subunits with alpha subunits is consistent with the alpha4betan model, where n equals 0, 1, 2, 3, or 4, depending upon the relative concentration of alpha and beta subunits. The alpha4betan stoichiometry allows for gradual changes of the Kvbeta1-mediated inactivation. In contrast, Kvbeta2 subunits self-associate to form oligomers and interact with the alpha subunits via alpha4beta4 stoichiometry, which permits effective multivalent associations with alpha subunits. Such distinct functional stoichiometry of Kvbeta1 and Kvbeta2 provides a molecular mechanism that is well suited to their contrasting activities of up-regulation or down-regulation of potassium currents.
authors.affiliation: Department of Physiology, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.forename: W
authors.initials: W
authors.lastname: Yu
authors.forename: J M
authors.initials: JM
authors.lastname: Wright
authors.forename: R W
authors.initials: RW
authors.lastname: Raab
authors.forename: M
authors.initials: M
authors.lastname: Li
mesh_terms: D000818:Animals; D019556:COS Cells; D019281:Dimerization; D046911:Macromolecular Substances; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017384:Sequence Deletion; D051637:Shaker Superfamily of Potassium Channels; D013329:Structure-Activity Relationship
chemical_list: D046911:Macromolecular Substances; D015221:Potassium Channels; D051637:Shaker Superfamily of Potassium Channels